The majority (70-90%) of renal transplant patients have evidence of viral infection, usually with cytomegalovirus (CMV), during the first 6 months post-transplant. Preliminary, mostly retrospective studies at our institution and elsewhere have indicated an association between viral infections and acute febrile illnesses, transplant rejection and mortality. However, answers are needed to the questions 1) what is the source of the patient's virus? 2) do viruses cause clinically important illness? 3) how do viral infections affect immune function and relate to episodes of transplant rejection? 4) do viruses other than CMV play a significant role? Our objective is to answer these questions by performing an intensive prospective epidemiologic viral study. The source of virus will be sought by culturing donors, donor organs, transplant staff, and blood products which the patients receive. CMV isolates and patient sera will be studied for strain specificity which might indicate whether CMV infections are exogenous or reactivation of latent infection. The relationship of viral shedding with serious clinical illness will be examined by prospective studies of the patients with frequent viral culturing and detailed clinical observations. Nonspecific and specific humoral and cell-mediated tests will be done to examine the relationship of viral infection to immune function, and these studies will be correlated with episodes of rejection. The tests include quantitation of T and B cells, a battery of viral antibody titers with emphasis on herpesviruses, mitogen stimulation using PHA, Con A, and CMV antigen, mixed lymphocyte culture, lymphocyte mediated cytotoxicity toward CMV antigen, and allogeneic induced CMV release from patient lymphocytes. The virologic technics will enable us to study the role of viruses other than CMV. These studies have broad implications for elucidating the etiology and managing episodes of transplant rejection, and for providing appropriate epidemiologic, prophylactic and therapeutic approaches for the prevention or treatment of virus infections in renal transplant patients.